Brainstem Control of Subcortical Visual Information

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DESCRIPTION (provided by applicant): The dorsal lateral geniculate nucleus (LGN) is a vital link in the chain of perception. Retinal ganglion cells encode the visual world and transmit it to the LGN. Most agree that gating of this information occurs at the retinogeniculate synapse, but a complete mechanism is elusive. Our recent findings demonstrate several new and exciting sources of dynamic control of visual information at the LGN. Two of these are known modulators of relay neurons: the cholinergic parabrachial brainstem (PBR) and the massive corticogeniculate (CG) feedback. The PBR releases nitric oxide (NO), and our data indicate an amazing difference in the way NO affects retinal and cortical inputs. NO has a powerful and selective inhibitory influence on retinogeniculate transmission in the LGN through interaction with the NMDA receptor; however, transmission through the CG pathway is enhanced by two separate mechanisms. The other great remaining mystery of thalamic function is the purpose of the cortical feedback to LGN from layer 6, which we now see as intimately linked with the PBR and NO. We propose a new series of experiments to reveal the contributions of the PBR, and cortical feedback influences, with a global hypothesis that vision requires cooperative activity patterns of both of these pathways. Aim 1: How does NO affect LGN relay cell membrane properties? NO suppresses NMDA receptor function in the retinogeniculate pathway. We hypothesize that NO also targets the low threshold Ca2+ current (I(T)) and a key K+ currents (I) (As)). We will probe I(T) and I(As) with intracellular patch recordings from slices of the LGN, while delivering NO donors and scavengers, and by stimulating intrinsic NO production through the enzyme bNOS. Aim 2: How does NO affect fast synaptic inputs to LGN relay cells? We will stimulate the retinal and CG pathways (to evoke GABAergic IPSP/JPSCs) and the CG pathway (to evoke glutamatergic EPSP/EPSCs) in slices while manipulating NO levels. We hypothesize a stark difference in how NO affects retinal and cortical EPSP/EPSCs; cortical EPSP/EPSCs are enhanced, indicating that the PBR, through NO, may shift the balance away from retinal feedforward processing and toward cortical feedback processing. Aim 3: How does the corticogeniculate projection control the thalamocortical dialog? Relay cells respond to retinal inputs in one of two modes, burst or tonic. We hypothesize that layer 6 promotes a visuotopic gradient of burst and tonic responses, and synchronous firing, in the LGN. We will record from thalamic ensembles during visual processing, while activating and inactivating layer 6 of visual cortex, and while activating brainstem pathways. The impact of retinal inputs to LGN is well known, but the field is struggling with the nature and scope of extraretinal synaptic influences. The answers to these questions will completely transform our view of thalamic function from that of a slave of the periphery to a partner with cortex in binding together the threads of visual perception.